Genetic and Genomic Characterization of 462 Melanoma Patient-Derived Xenografts, Tumor Biopsies, and Cell Lines

• DOI: 10.1016/j.celrep.2017.10.052
• Publication Date: 2017-11-14T16:06:27Z
• Authors: Bradley Garman; Ioannis N. Anasto...; Clemens Krepler; Patricia Brafford; Katrin Sproesser; Yuchao Jiang; Bradley Wubbenhorst; Ravi Amaravadi; Joseph Bennett; Marilda Beqiri; David Elder; Keith T. Flaherty; Dennie T. Frederick; Tara C. Gangadhar; Michael Guarino; David Hoon; Giorgos Karakousis; Qin Liu; Nandita Mitra; Nicholas J. Petrelli; Lynn Schuchter; Batool Shannan; Carol L. Shields; Jennifer Wargo; Brandon Wenz; Melissa A. Wilson; Min Xiao; Wei Xu; Xaiowei Xu; Xiangfan Yin; Nancy R. Zhang; Michael A. Davies; Meenhard Herlyn; Katherine L. Nath...
• Keywords: Adult; Male; 0301 basic medicine; 570; QH301-705.5; MAP Kinase Signaling System; 610; cell lines; Mice; 03 medical and health sciences; Cell Line, Tumor; melanoma; Medicine and Health Sciences; Animals; Humans; Biology (General); Melanoma; Aged; Repetitive Sequences, Nucleic Acid; Aged, 80 and over; Genome; massively parallel sequencing; Oncogenes; Middle Aged; 3. Good health; Oncology; Mutation; Heterografts; Surgery; Female; patient-derived xenografts

Tumor-sequencing studies have revealed the widespread genetic diversity of melanoma. Sequencing of 108 genes previously implicated in melanomagenesis was performed on 462 patient-derived xenografts (PDXs), cell lines, and tumors to identify mutational and copy number aberrations. Samples came from 371 unique individuals: 263 were naive to treatment, and 108 were previously treated with targeted therapy (34), immunotherapy (54), or both (20). Models of all previously reported major melanoma subtypes (BRAF, NRAS, NF1, KIT, and WT/WT/WT) were identified. Multiple minor melanoma subtypes were also recapitulated, including melanomas with multiple activating mutations in the MAPK-signaling pathway and chromatin-remodeling gene mutations. These well-characterized melanoma PDXs and cell lines can be used not only as reagents for a large array of biological studies but also as pre-clinical models to facilitate drug development.